Table 2 Summary of publication year, reference (Ref.), painful procedures/condition/disease, grouping and age of animals, sampling times, Substance P (SP) concentrations and conclusion of 25 studies using SP for the evaluation of nociception in calves. The administration of local anesthesia (LA) is given in the same column as the grouping of animals. In 32% (n = 8), no extractable data was presented
Year | Ref | Procedure/Disease with/without LA | Grouping | Age/Weight | Sampling Times and Assay Platform | SP Concentrations | Conclusions |
|---|---|---|---|---|---|---|---|
Castration | |||||||
2008 | [8] | Surgical Castration | - Surgical Castration (n = 5) - Sham Castration (n = 5) - no LA | 4 to 6 months | - Baseline (24 and 12 h before procedure) - immediately after procedure - 10, 20, 30 and 45 min after procedure - 1, 1.5, 2, 2.5, 4 and 4 h after procedure - Competitive Immunoassay | Mean and SEM plasma SP Concentrations Surgical Castration Cmin 303.98 ± 119.73 pg/mL Cmax 888.92 ± 235.44 pg/mL Sham Castration Cmin 88.68 ± 23.93 pg/mL Cmax 691.38 ± 71.83 pg/ml | Castrated calves showed significantly (p = 0.042) greater mean plasma SP concentrations for all time points after castration or simulated castration than sham castrated calves. Clear between- and within- calf variations of SP throughout the study period were observed |
2013 | [19] | Band castration Cut-and-Clamp Cut-and-Pull | - CONT (control, n = 20) - BAND (n = 18) - CLAMP (n = 20) - PULL (n = 18) - no LA | 8 weeks (n = 40) 6 months (n = 40) | - Baseline - 60, 120, 240, 480, and 5760 min after castration - Competitive Immunoassay | No extractable numerical data | SP concentrations differed significantly (p = 0.01) by age; regardless of the method of castration, 6-months-old calves showed higher SP concentrations relative to 8-week-old calves |
[30] | Band Castration | - BAND (n = 7) - BAND-MEL (n = 7, castration and meloxicam) - SHAM (n = 7, sham castration) - no LA | 300.8 ± 4.96 kg | - Day 0 - Day 1 - Day 7 of trial - Competitive Immunoassay | LSM plasma SP Concentrations BAND, Day 0 143.05 pg/mL BAND, Day 1 167.24 pg/mL BAND-MEL, Day 0 158.69 pg/mL BAND-MEL, Day 1 159.66 pg/mL SHAM, Day 0 166.36 pg/mL SHAM, Day 1 151.45 pg/mL | There was no difference in plasma SP concentrations across treatments; meloxicam was administered on days -1, 0, and 1 in a dose of 1.0, 0.5, and 0.5 mg/kg BW respectively | |
2014 | [31] | Surgical Castration | - Flunixine (n = 24) - Placebo (n = 24) - ring block of 2% lidocaine for both groups | 25 ± 2 days | - directly before treatment with NSAID/Placebo - days 1, 2, 3, 7, 14, 21, 28, 35, and 49 - RIA | Mean and SE plasma SP Concentrations Flunixine 34 ± 1.1 pg/mL Saline 34 ± 1.1 pg/mL Baseline 41 ± 1.2 pg/mL Day 3 34 ± 1.2 pg/mL Day 21 30 ± 1.2 pg/mL | An effect of day on serum SP concentrations was observed (p < 0.001). SP concentrations were highest at baseline, dropped by day 3, and leveled out by day 21. The application of flunixin meglumine (1.1 mg/kg BW IV) had no effect on the serum SP concentrations; also, there was no interaction between drug an day |
2016 | [10] | Band Castration Surgical Castration | for both castration methods each - Meloxicam (n = 15) - Control (n = 15) - no LA | 4 to 5 months | - Day -2 - 5, 24, 48, and 72 h following castration - Competitive Enzyme Immunoassay | Mean and SE plasma SP Concentrations Day -1 Band, Meloxicam 243.9 ± 16.4 pg/mL Band, Control 268.2 ± 15.6 pg/mL Surgical, Meloxicam 249.8 ± 7.8 pg/mL Surgical, Control 244.5 ± 11.5 pg/mL Day 0 Band, Meloxicam 243.7 ± 13.9 pg/mL Band, Control 340.5 ± 23.0 pg/mL Surgical, Meloxicam 267.9 ± 11.2 pg/mL Surgical, Control 314.7 ± 13.4 pg/mL Day 1 Band, Meloxicam 261.8 ± 15.5 pg/mL Band, Control 335.5 ± 23.8 pg/mL Surgical, Meloxicam 260.6 ± 8.1 pg/mL Surgical, Control 304.4 ± 17.0 pg/mL Day 2 Band, Meloxicam 251.6 ± 14.9 pg/mL Band, Control 295.2 ± 16.3 pg/mL Surgical, Meloxicam 273.2 ± 10.4 pg/mL Surgical, Control 301.1 ± 17.0 pg/mL Day 3 Band, Meloxicam 253.7 ± 12.7 pg/mL Band, Control 264.9 ± 16.4 pg/mL Surgical, Meloxicam 333.7 ± 11.2 pg/mL Surgical, Control 334.8 ± 5.3 pg/mL | Plasma SP concentrations were significantly (p < 0.05) higher in control compared with meloxicam (1 mg/kg BW orally) treated animals, both on day 0 and day 1 and both for band as well as surgically castrated calves |
2017 | [32] | Band Castration Knife Castration | - CT (sham castration) - BA (band castration) - KN (knife castration) - no LA | 12 calves each per group 1 week (n = 36) 2 months (n = 36) 4 months (n = 36) | - Baseline (D-1), immediately before castration - weekly afterwards until end of trial (= sloughing off of testicles of banded calves) - RIA | SP concentrations 1 week old Control 60.6 pg/mL Band Castration 63.9 pg/mL Knife Castration 62.0 pg/mL 2 months old Control 80.1 pg/mL Band Castration 76.2 pg/mL Knife Castration 81.0 pg/mL 4 months old Control 103.3 pg/mL Band Castration 100.3 pg/mL Knife Castration 100.0 pg/mL | There was no effect of treatment on SP concentrations in 1-week, 2-months, and 4-months old calves |
[33] | Band Castration Knife Castration | - CT (sham castration) - BA (band castration) - KN (knife castration) - no LA | 12 calves each per group 1 week (n = 36) 2 months (n = 36) 4 months (n = 36) | - Baseline (D-1) - T0, 60, and 120 Minutes after castration - 7 days (D7) after castration - RIA | LSM serum SP Concentrations Day 0 and 7 after castration 1 week old: Control 92.6 pg/mL Band Castration 108.7 pg/mL Knife Castration 100.6 pg/mL 2 months old: Control 73.5 pg/mL Band Castration 70.1 pg/mL Knife Castration 66.8 pg/mL 4 months old: Control 102.9 pg/mL Band Castration 101.8 pg/mL Knife Castration 102.5 pg/mL 0, 60, 120 min after castration 1 week old: Control 72.1 pg/mL Band Castration 69.8 pg/mL Knife Castration 68.0 pg/mL 2 months old: Control 72.2 pg/mL Band Castration 70.6 pg/mL Knife Castration 68.9 pg/mL 4 months old: Control 103.5 pg/mL Band Castration 101.5 pg/mL Knife Castration 101.1 pg/mL | There was no treatment or interaction effect for SP in 1-week-old calves No treatment differences were seen for SP following castration in 2-months and 4-months-old calves | |
[5] | Knife Castration | - 6H (NSAID 6 h prior), n = 11) - 3H (NSAID 3 h prior, n = 12) - 0H (NSAID 0 h prior, n = 11) - no LA | 7 to 8 months | -D-7, D-5, D-2, D-1 before castration - immediately before castration (T0) - 30, 60, 120 and 240 min, after castration - 1, 2, 5, 7, 14, 21, and 28 days after castration - RIA | No extractable numerical data | There was no treatment or interaction effects for SP on the day of castration, but an overall increase in SP concentrations (p < 0.01) On days 1 to 28 after castration, there was a treatment x time interaction for SP (p = 0.01), with 6H and 3H calves (which received 0.5 mg/kg BW meloxicam SC 6 or 3 h prior to surgery, respectively) showing higher SP concentrations than 0H calves on day 1 after castration; 5 days following castration, SP concentrations tended to be higher in 3H compared with 6H calves | |
2018 | [20] | Surgical Castration | - CAST + FLU (flunixin meglumine, n = 8) - CAST + PLBO (placebo, n = 8) - SHAM + PLBO (placebo, n = 8) - no LA | 9 months | - Baseline on the morning of experiment - 1, 2, 4, 6, 8, 12, 24, 48, and 72 h after treatment application - RIA | No extractable numerical data | Following castration, there was no effect of topical flunixin meglumine (3.33 mg/kg BW) on SP concentrations. Also, there was no time effect or treatment by time interaction between the groups |
[34] | Band Castration Knife Castration | - CT (control, n = 24) - BA (band, n = 24) - KN (knife, n = 24) and in each group - NM (placebo, n = 36) - M (Meloxicam, n = 36) - no LA | 7 to 8 days | - Day -1 - T0, 60, 90, and 120 min after castration - day 1, 2, 3, and 7 after castration - RIA | LSM serum SP Concentrations Minutes after castration Control, NM97.1 pg/mL Control, M 103.1 Band, NM 101.7 pg/mL Band, M 93.4 pg/mL Knife, NM 102.7 pg/mL Knife, M 99.5 pg/mL Days after castration Control, NM 92.3 pg/mL Control, M 99.1 pg/mL Band, NM 100.2 pg/mL Band, M 91.7 pg/mL Knife, NM 99.1 pg/mL Knife, M 90.1 pg/mL | There was a trend (p = 0.09) for SP concentrations to be higher in NM compared with M (meloxicam at 0.5 mg/kg SC) calves 120 min after castration. Also, SP concentrations were higher (p = 0.04) on day 7, and tended to be higher (p = 0.08) on day 3 after castration in NM than in M calves There was also a trend (p = 0.06) for SP concentrations to be higher in CT-M, BA-NM, KN-NM calves than BA-M and KN-M calves | |
[35] | Knife Castration Branding | - CT (SHAM, n = 23) - KN (knife, n = 24) - BK (branding and knife, n = 24) and in each group - NM (placebo, n = 36) - M (Meloxicam, n = 36) - no LA | 67 to 87 days | - 24 h (Day -1) before castration - immediately before (T0) castration - 60, 90, 120, 180 min after castration - day 1, 2, 3, and 7 after castration -RIA | LSM serum SP Concentrations Minutes after castration Control 81.8 pg/mL Knife, NM 80.1 pg/mL Knife, M 79.4 pg/mL Branding + Knife, NM 82.6 pg/mL Branding + Knife, M 70.0 pg/mL Days after castration Control 82.2 pg/mL Knife, NM 78.7 pg/mL Knife, M 75.8 pg/mL Branding + Knife, NM 84.5 pg/mL Branding + Knife, M 81.4 pg/mL | There was no effect of procedure of medication (Meloxicam, 0.5 mg/kg SC) for SP at any time after the procedure | |
[36] | Surgical Castration | - NC-NLF (no castration, no analgesia, n = 10) - NC-LF (no castration, analgesia, n = 10) - C-NLF (castration, no analgesia, n = 10) - C-LF (castration, analgesia, n = 10) -ring block with 2% lidocaine hydrochloride for LF treatments | 6.3 ± 0.09 months | - Immediately before castration - 0.5 and 6 h after castration - 1, 3, and 7 days after castration - ELISA | Plasma SP Concentrations 6 h following castration C-NLF 3.09 ng/mL NC-NLF 0.74 ng/mL Otherwise, no extractable numerical data | SP concentrations did not differ between groups 30 min after castration; at 6 h after castration, SP concentrations were significantly (p = 0.03) higher in C-NLF compared with C-LF (Castration with 12 ml lidocaine and 0.5 mg/kg BW flunixin meglumine) (3.09 ng/mL and 0.74 ng/mL respectively); SP concentrations returned to baseline values from day 1 on | |
2019 | [37] | Knife Castration | - PO (Meloxicam, 1 mg/kg—BW orally, n = 12) - SC (Meloxicam, 0.5 mg/kg—BW SC, n = 11) - no LA | 7 to 8 months | - Day -2 and -1 before castration - T0, and 30, 60, 90, 120, 150, and 240 min after castration - day 1, 2, 3, 5, 7, 10, 14, 21, and 29 after castration - RIA | LSM serum SP Concentrations PO 83.0 pg/mL SC 78.7 pg/mL | SP concentrations were higher (p ≤ 0.05) in PO compared with SC calves |
2021 | [38] | Surgical Castration | - SHAM (castration), followed by - CAST (24 h later) - no LA | 6 weeks (n = 10) 3 months (n = 10) 6 months (n = 10) | - Immediately prior to both procedures (Time 0) - 1, 2, 4, 8, and 12 h after the procedures - Competitive Immunoassay | No extractable numerical data | At later recovery times, SP concentrations were lower in CAST compared with SHAM. Younger calves (6 weeks old) showed lower SP concentrations in CAST than in SHAM (p = 0.0174) |
Dehorning | |||||||
2012 | [39] | Scoop Dehorning | - Meloxicam (n = 6) - Placebo (n = 6) - no LA | 16 to 20 weeks | - Baseline (prior to drug or placebo administration) - 5, 10, 15, 29, 30, and 60 min afterwards - 6, 22, 30, 45, and 52 h afterwards - ELISA | Mean and SEM plasma SP concentrations Placebo 114.70 ± 30.84 pg/mL Meloxicam 71.36 ± 20.84 pg/mL | Mean SP concentrations were significantly (p = 0.038) lower in meloxicam (0.5 mg/kg IV) treated compared with control calves. Plasma SP concentrations were estimated to be 0.5 less in the presence than in the absence of meloxicam treatment |
2013 | [40] | Cautery Dehorning | - MEL-PRE (NSAID pre-OP, n = 10) - MEL-POST (NSAID post-OP, n = 10) - CONT (control, n = 10) - cornual nerve block with 2% lidocaine hydrochloride for all groups | 8 to 10 weeks | - 2 h before procedure (baseline) - 5, 30, 60, 120, 240, 360, 480, and 720 min after dehorning - Competitive Immunoassay | No extractable numerical data | At 120 min after dehorning, calves which received meloxicam (1 mg/kg orally) had significantly (p = 0.039) lower SP concentrations than control calves |
[41] | Scoop dehorning | - CONT (placebo, n = 8) - MEL (meloxicam, n = 8) - GBP (gabapentin, n = 8) - MEL + GBP (n = 8) - FLU (flunixin meglumine, n = 8) - cornual nerve block with 2% lidocaine hydrochloride for all groups | 6 months | - Baseline (-10 min) before dehorning - 5 min after dehorning - 0.5, 1, 2, 4, 6, 8, and 12 h after dehorning - Competitive Immunoassay | Mean and SD plasma SP concentrations Calves not treated with Analgesia 137.29 ± 42.97 pg/mL Calves treated with Analgesia 63.35 ± 21.25 pg/mL | No differences between treatment groups (Placebo, Meloxicam (1 mg/kg) orally, Gabapentin capsules (15 mg/kg) orally, Meloxicam and Gabapentin orally, or Flunixine meglumine (2.2 mg/kg) IV) were found. Mean plasma SP concentrations were significantly (p = 0.02) lower in calves treated with analgesics compared with control calves | |
2015 | [21] | Cautery Disbudding | - FIROCOXIB (NSAID, n = 10) - PLACEBO (n = 10) - cornual nerve block with 2% lidocaine hydrochloride | 32.9 ± 3.9 days | - Baseline (1.5 h prior to dehorning) - 15 and 30 min, after dehorning - 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, and 96 h after dehorning - RIA | LSM and SE of plasma SP concentrations FIROCOXIB 22.7 ± 0.7 pg/mL PLACEBO 20.8 ± 0.4 pg/mL | SP concentrations were not different between placebo and firocoxib (0.5 mg/kg orally) treated calves. There was no effect of time or time x treatment in the 96 h sampling period |
2016 | [42] | Cautery Dehorning | - SHAM (n = 10) - PO (NSAID orally, n = 10) - SQ (NSAID SC, n = 10) - PLCBO (placebo, n = 10) - cornual nerve block with 2% lidocaine hydrochloride | 50.9 ± 5.3 days | - Baseline (1 h prior to drug administration) - 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, and 96 h after dehorning - RIA | Mean plasma SP Concentrations with 95% CI Control PLCBO 17.0 pg/mL (14.8 – 19.5) SHAM 16.4 pg/mL (14.3 – 18.9) Carprofen PO 17.0 pg/mL (14.8 – 19.5) SQ 16.3 pg/mL (14.2 – 18.07) | No effect of treatment (carprofen, 1.4 mg/kg BW, either orally or SC), time, or time and treatment on SP concentrations. SP concentrations were greater (0.11 ± 0.039 pg/mL) in female than male calves (p = 0.005) |
2017 | [43] | Cautery Dehorning | - DH-FLU (dehorning and NSAID, n = 8) - SHAM-FLU (sham dehorning and NSAID, n = 8) - DH-PLBO (dehorning and placebo, n = 8) - no LA | 6 to 8 weeks | - Baseline on the morning of experiment - 1, 2, 4, 12, 24, and 48 h after treatment application - RIA | Mean plasma SP Concentrations with 95% CI DH-FLU 103.5 pg/mL (92.7 – 114.4) SHAM-FLU (99.7 pg/mL (94.3 – 105.2) DH-PLBO 104.6 (96.2 – 113.1) | No effect of treament with topical flunixine meglumine (3.33 mg/kg) for SP concentrations |
2019 | [44] | Dehorning with Caustic Paste | - M1 (NSAID followed by placebo 24 h later, n = 15) - M2 (NSAID twice in 24 h, n = 15) - CONTROL (n = 16) - SHAM (sham disbudding, n = 15) - no LA | 3 days | - Baseline (5 min prior to disbudding) - 24, 48, 72, and 96 h after disbudding - RIA | LSM plasma SP Concentrations Control 164.47 pg/mL Sham 198.53 pg/mL M1 144.50 pg/mL M2 144.74 pg/mL | Plasma SP concentrations not different between plasma SP concentrations between CONTROL and M2 (45 mg Meloxicam orally 24 h apart) than SHAM or M1 (45 mg Meloxicam orally, followed by placebo). Calves in SHAM had significantly (p < 0.0001) higher plasma SP concentrations |
Other | |||||||
2013 | [45] | Infection with Mannheimia haemolytica i | - MH (infected calves, n = 10) - CN (control, n = 8) - no LA | 240.0 ± 13.1 kg | - Before challenge (D0) - 12 h after inoculation - day 1, 2, 3, 7, and 9 after inoculation - Immunoassay Kit (ELISA) | No extractable numerical data | There was a significant (p < 0.05) interaction between treatment group and trial day for SP concentrations. SP concentrations were significantly increased in MH compared with CT calves on D0.5 and decreased to average concentrations on D7 |
2018 | [18] | Umbilical Surgery | - CON (meloxicam treated calves, n = 10) - MET (metamizole and meloxicam treated calves, n = 11) - no LA | 37 ± 8 days | - Baseline (-1 h) before surgery - 5, 15, 30, 45, 90, 150, and 510 min after start of surgery (skin incision) - ELISA | Median plasma SP Concentrations Baseline CON 690.0 pg/mL (lower quartile 497.0 pg/mL; upper quartile 1301.1 pg/mL) MET 560.3 pg/ml (lower quartile 328.7 pg/mL; upper quartile 572.6 pg/mL CON T + 5 986.8 pg/mL T + 30 1217.2 pg/mL MET T + 60 541.1 pg/mL T + 150 555.6 pg/mL T + 510: 547.5 pg/ mL | Plasma SP concentrations were lower in MET (40 mg/kg BW metamizole IV and 0.5 mg/kg BW meloxicam IV) compared with CON (0.5 mg/kg BW meloxicam IV) at all times during and after surgery. In CON, plasma SP concentrations were significantly different from baselines at T5 (p = 0.027), T30 (p = 0.006) and T90 (p = 0.02). Calves of CON did not reach baseline plasma SP concentrations during the trial period |
2019 | [46] | Assisted Calving | - Meloxicam (n = 17) - Placebo (n = 16) | Newborn | - Birth (within 10 min of delivery) - 1, 4, 24 h and 7 and 10 days after delivery - RIA | No extractable numerical data | There was no significant difference between placebo and meloxicam (0.5 mg/kg BW SC) treated calves for SP concentrations over the 24-h period |
2020 | [47] | Tail Docking | - A (Amputation, n = 8) - K (Control, n = 8) - no LA | 8 to 10 weeks | - D-2 to Day 2 at 11:10 am daily - D0 at 08:10 AM prior to tail docking via rubber ring - ELISA | No extractable numerical data | There was a trend (p = 0.087) for a difference between A and K for the mean SP concentrations. After differentiation of values after tail docking and handling, there was no difference in SP concentrations between groups |